An oral cephem agent, cefditoren pivoxil of the formula (4), is in wide used as an antibacterial agent having a broad antimicrobial spectrum and strong antibacterial activities.

With cephalosporin antibiotics having alkenyl at the 3-position, the steric structure of the alkenyl group at the 3-position has Z configuration as is the case with cefditoren pivoxil. The mechanism of producing outstanding antibacterial activities on gram-negative bacteria is attributable partly to this feature. For the antibacterial pharmaceutical agent to exhibit its effect, therefore, it is important to diminish to the greatest possible extent the presence of the geometrical E-isomer of cefditoren pivoxil. In preparing cefditoren pivoxil, attempts have been made to improve the Z-isomer content of process intermediates.
For example, a process has been disclosed for preparing an amine salt of Z/E mixture of 7-amino-3-[2-(4-methylthiazol-5-yl)vinyl]-3-cephem-4-carboxylic acid, a process intermediate and depleting the amine salt of 7-amino-3-[(E)-2-(4-methylthiazol-5-yl)vinyl]-3-cephem-4-carboxylic acid by crystallization (see, for example, Patent Literature 1).
[Patent Literature 1] JP1995-188250 A
The process disclosed in the literature, however, is not satisfactory in the yields of the desired 7-amino-3-[2-(4-methylthiazol-5-yl)vinyl]-3-cephem-4-carboxylic acid and the salt thereof which are depleted in the E-isomer content, and the amine salt can not be filtered off efficiently. Thus, the process can not be said to be a suitable process from an economical viewpoint (see Comparative Example 1).
An object of the present invention is to provide a 3-alkenylcephem compound useful as an intermediate in the process for preparing cefditoren pivoxil which is in wide use as an excellent antibacterial agent.
Another object of the invention is to provide an economically outstanding and industrially suitable process for preparing a 3-alkenylcephem compound which is improved in Z-isomer content.